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A catalog of genetic loci associated with kidney function from analyses of a million individuals
(2019)
Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
This work is focused on the influence of an ionic liquid (IL), i.e. ethyl-methylimidazolium hexylsulfate, on the spontaneous formation of microemulsions with ionic surfactants. The influence of the ionic liquid on Structure formation in the optically clear phase region in water/toluene/pentanol mixtures in presence of the cationic surfactant CTAB was studied in more detail. The results show a significant increase of the transparent phase region by adding the ionic liquid. Conductometric investigations demonstrate that adding the ionic liquid can drastically reduce the droplet- droplet interactions in the L-2 phase. H-1 nuclear magnetic resonance (H-1 NMR) diffusion coefficient measurements in combination with dynamic light scattering measurements clearly show that inverse microemulsion droplets still exist, but the droplet size is decreased to 2 nm. A more detailed characterisation of the isotropic phase channel by means of conductivity measurements, dynamic light scattering (DLS), H-1 NMR and cryo-scanning electron microscopy (SEM), allows the identification of a bicontinuous sponge phase between the L-1 and L-2 phase. When the poly(ethyleneimine) is added, the isotropic phase range is reduced drastically, but the inverse microemulsion range still exists.
Biological responses to climate change have been widely documented across taxa and regions, but it remains unclear whether species are maintaining a good match between phenotype and environment, i.e. whether observed trait changes are adaptive. Here we reviewed 10,090 abstracts and extracted data from 71 studies reported in 58 relevant publications, to assess quantitatively whether phenotypic trait changes associated with climate change are adaptive in animals. A meta-analysis focussing on birds, the taxon best represented in our dataset, suggests that global warming has not systematically affected morphological traits, but has advanced phenological traits. We demonstrate that these advances are adaptive for some species, but imperfect as evidenced by the observed consistent selection for earlier timing. Application of a theoretical model indicates that the evolutionary load imposed by incomplete adaptive responses to ongoing climate change may already be threatening the persistence of species.
Background:
It has previously been shown that conditioning activities consisting of repetitive hops have the
potential to induce better drop jump (DJ) performance in recreationally active individuals. In the present pilot study,
we investigated whether repetitive conditioning hops can also increase reactive jump and sprint performance in
sprint-trained elite athletes competing at an international level.
Methods:
Jump and sprint performances of 5 athletes were randomly assessed under 2 conditions. The control
condition (CON) comprised 8 DJs and 4 trials of 30-m sprints. The intervention condition (HOP) consisted of 10
maximal repetitive two-legged hops that were conducted 10 s prior to each single DJ and sprint trial. DJ
performance was analyzed using a one-dimensional ground reaction force plate. Step length (SL), contact time (CT),
and sprint time (ST) during the 30-m sprints were recorded using an opto-electronic measurement system.
Results:
Following the conditioning activity, DJ height and external DJ peak power were both significantly
increased by 11 % compared to the control condition. All other variables did not show any significant differences
between HOP and CON.
Conclusions:
In the present pilot study, we were able to demonstrate large improvements in DJ performance even
in sprint-trained elite athletes following a conditioning activity consisting of maximal two-legged repetitive hops.
This strengthens the hypothesis that plyometric conditioning exercises can induce performance enhancements in
elite athletes that are even greater than those observed in recreationally active athletes.. In addition, it appears that
the transfer of these effects to other stretch-shortening cycle activities is limited, as we did not observe any
changes in sprint performance following the plyometric conditioning activity.
Background: It has previously been shown that conditioning activities consisting of repetitive hops have the potential to induce better drop jump (DJ) performance in recreationally active individuals. In the present pilot study, we investigated whether repetitive conditioning hops can also increase reactive jump and sprint performance in sprint-trained elite athletes competing at an international level. Methods: Jump and sprint performances of 5 athletes were randomly assessed under 2 conditions. The control condition (CON) comprised 8 DJs and 4 trials of 30-m sprints. The intervention condition (HOP) consisted of 10 maximal repetitive two-legged hops that were conducted 10 s prior to each single DJ and sprint trial. DJ performance was analyzed using a one-dimensional ground reaction force plate. Step length (SL), contact time (CT), and sprint time (ST) during the 30-m sprints were recorded using an opto-electronic measurement system. Results: Following the conditioning activity, DJ height and external DJ peak power were both significantly increased by 11 % compared to the control condition. All other variables did not show any significant differences between HOP and CON. Conclusions: In the present pilot study, we were able to demonstrate large improvements in DJ performance even in sprint-trained elite athletes following a conditioning activity consisting of maximal two-legged repetitive hops. This strengthens the hypothesis that plyometric conditioning exercises can induce performance enhancements in elite athletes that are even greater than those observed in recreationally active athletes.. In addition, it appears that the transfer of these effects to other stretch-shortening cycle activities is limited, as we did not observe any changes in sprint performance following the plyometric conditioning activity.
Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m(2)/year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m(2) at follow-up among those with eGFRcrea 60 mL/min/1.73m(2) or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or (LARP4B). Individuals at high compared to those at low genetic risk (8-14 vs. 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function.
Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m(2)/year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m(2) at follow-up among those with eGFRcrea 60 mL/min/1.73m(2) or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or (LARP4B). Individuals at high compared to those at low genetic risk (8-14 vs. 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function.
This paper is focused on the influence of added polyampholyte, namely poly(N,N;-diallyl-N,N;- dimethyl-alt-maleamic carboxylate) on the inverse micellar phase range of the pseudo-ternary system consisting of toluene-pentanol (1:1)/SDS/water in dependence on the pH value and the temperature. Investigations on phase behavior have revealed that a greater extension in direction to the water-rich corner can be found at pH 4 compared to pH 9. In order to understand changes in the microstructure, polymer-surfactant interactions in dependence on pH have been examined by means of diffusion-ordered spectroscopy, differential scanning calorimetry, as well as conductivity measurements. The results have proven that the present microemulsion consists of water-in-oil droplets, with the polyampholyte located more in the inner core of the water droplets at pH 9 rather than at the interphase of the surfactant film at pH 4.